In the United States, approximately 30,000 people die of pancreatic cancer each year. Among cancers of the gastrointestinal tract, it is the third most common malignancy and the fifth leading cause of cancer-related mortality overall. The disease is difficult to diagnose in its early stages, and almost 90% of patients have incurable disease by the time they present with symptoms. The overall 5-year survival rate for this disease is less than 5%, so mortality rates approach incidence rates. The only treatment that offers a survival advantage is surgical resection. To date, no effective therapies exist for patients with inoperable disease (locally advanced or metastatic pancreatic cancer). This is a phase II clinical trial that combines two novel therapies for solid tumors in patients with inoperable pancreatic cancer--TNFerade to induce apoptosis and dendritic cell therapy to induce an immunlogic response. Each therapy has been shown to individually affect the growth of pancreatic adenocarcinoma and clinical outcomes in patients with this disease. The combination of these therapies has never been proposed or executed in this clinical setting, but animal models show a therapeutic synergy that leads to tumor regression and protection against subsequent challenge with the same tumor type. The long term and broad objectives of this project are to determine whether a lasting immune response can be induced in patients with pancreatic cancer using autologous dendritic cells pulsed with keyhole limpit hemocyanin after the induction of apoptosis in the primary tumors with an adenoviral vector coding for human tumor necrosis factor-alpha (TNFerade). The specific aims of this project are as follows: 1) To establish the feasability and safety of intratumoral injections of activated dendritic cells combined with TNFerade in the treatment of locally advanced / metastatic pancreatic cancer; 2) To determine the immunologic and anti-tumor effects of DC combined with TNFerade in patients with advanced pancreatic malignancy; 3) To determine the effect of TNFerade on the local microenvironment after injection and activation. Patients with inoperable tumors will be enrolled to receive the treatment protocol. The tumors will be evaluated for the degree of apoptosis, and the patients will be investigated for a systemic response to tumor associated antigens. [unreadable] [unreadable] [unreadable]